Multiplex Protein Imaging with Secondary Ion Mass Spectrometry Using Metal Oxide Nanoparticle-Conjugated Antibodies

Dae Won Moon, Young Ho Park, Sun Young Lee, Heejin Lim, Su Hwa Kwak, Minseok S. Kim, Hyunmin Kim, Eunjoo Kim, Yebin Jung, Hyang Sook Hoe, Sungjee Kim, Dong Kwon Lim, Chul Hoon Kim, Su Il In

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


In spite of recent developments in mass spectrometry imaging techniques, high-resolution multiplex protein bioimaging techniques are required to unveil the complex inter- A nd intracellular biomolecular interactions for accurate understanding of life phenomena and disease mechanisms. Herein, we report multiplex protein imaging with secondary ion mass spectrometry (SIMS) using metal oxide nanoparticle (MONP)-conjugated antibodies with <300 nm spatial resolution in the low ion dose without ion beam damage because of the high secondary ion yields of the MONPs, which can provide simultaneous imaging of several proteins, especially from cell membranes. We applied our new imaging technique for the study of hippocampal tissue samples from control and Alzheimer's disease (AD) model mice; the proximity of protein clusters in the hippocampus CA1 region showed intriguing dependence on aging and AD progress, suggesting that protein cluster proximity may be helpful for understanding pathological pathways in the microscopic cellular level.

Original languageEnglish
Pages (from-to)18056-18064
Number of pages9
JournalACS Applied Materials and Interfaces
Issue number15
Publication statusPublished - 2020 Apr 15

Bibliographical note

Funding Information:
Technical supports on sample preparation by Y. J. Shin and HIM imaging from S. H. Heo are appreciated. This work was supported by the DGIST R&D Program of the Ministry of Science, ICT & Future Planning (18-BD-06) and National Research Foundation of Korea (2018R1A2A3075499), the Ministry of Science and ICT (2017R1E1A1A01074890 & 2017M2A2A6A01070912), and the KBRI Basic Research Program through the Korea Brain Research Institute funded by the Ministry of Science, ICT & Future Planning (grant number 19-BR-02-02, H.S.H.).

Publisher Copyright:
Copyright © 2020 American Chemical Society.


  • Alzheimer's disease
  • metal oxide nanoparticle
  • multiplex protein imaging
  • protein cluster proximity analysis
  • secondary ion mass spectrometry

ASJC Scopus subject areas

  • General Materials Science


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